Okikiolu AP, Ray S, Chakravarty K
… +8 more, Arimoro O, Martens R, Singh N, Ganesh A, Almekhlafi M, Hill MD, Menon BK, Sajobi TT
Int J Stroke
· 2026 Jun · PMID 41347705
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BACKGROUND: Randomized controlled trials (RCTs) have traditionally been designed with an explanatory approach, in contrast to incorporating real-world, pragmatic considerations. AIMS: This methodological review assesses...BACKGROUND: Randomized controlled trials (RCTs) have traditionally been designed with an explanatory approach, in contrast to incorporating real-world, pragmatic considerations. AIMS: This methodological review assesses the uptake of pragmatic designs in Phase III acute stroke RCTs. METHODS: We conducted a comprehensive literature search of the MEDLINE, Embase, and Cochrane Library databases from inception to 1 July 2024. Eligible articles included English-language published Phase III RCTs of acute ischemic stroke and intracerebral hemorrhage interventions. Using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) tool, each trial was rated on nine key domains, and relevant study characteristics were extracted. Trials with an average rating of 3 or higher, or a total score (sum of ratings) of 27 or higher (given that all domains were assessed), were considered to adopt an overall pragmatic approach to their design. Risk of bias was evaluated using the Cochrane risk of bias tool. RESULTS: Of the 5663 unique articles obtained after deduplication, 136 trials were included, and 71 (52%) trials were classified as pragmatic using the PRECIS-2 tool. A majority had a low risk of bias (63.2%). Pragmatic trials were more likely to be large sample, multicenter, multinational trials with broad inclusion criteria that cover multiple types of strokes. CONCLUSION: There has been an increased uptake of pragmatic designs in acute stroke over the last decade, reflecting improvements in acute stroke care and a greater consideration of real-world applicability by trialists.
Ismaiel M, Ahmed SR, Khalil MFE
… +13 more, Elmesallami AG, Ebied AAMK, Akl AZO, Kerolos YSS, Elshafei M, Khalil EHE, Daabis AMA, Yousef RA, Samy DM, Zehry H, Soliman AA, Khalil Ibrahim GAE, Zeinhom MG
Int J Stroke
· 2025 Dec · PMID 41328788
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INTRODUCTION: More intensive antiplatelet agents may reduce recurrent stroke risk in minor stroke and TIA, particularly those with non-cardioembolic stroke. The SOCRATES trial showed that ticagrelor was not superior to a...INTRODUCTION: More intensive antiplatelet agents may reduce recurrent stroke risk in minor stroke and TIA, particularly those with non-cardioembolic stroke. The SOCRATES trial showed that ticagrelor was not superior to aspirin in decreasing the risk of stroke, heart attack, or death at 90 days in patients with minor ischemic stroke or TIA. Cilostazol has been shown to have similar effects on platelet reactivity and aggregation to those produced by ticlopidine and aspirin, but may be associated with fewer hemorrhagic side effects. It is also cheaper than ticagrelor; for example, it is approximately half that of ticagrelor, making it a potentially cost-effective antiplatelet agent, especially in low and middle-income countries. AIM: To evaluate the benefits or hazards of adding cilostazol or ticagrelor to aspirin in patients with minor ischemic stroke or TIA. METHODS: We randomized 900 first-ever, large-vessel occlusion minor ischemic stroke or TIA patients in a one-to-one ratio to receive either a 200 mg loading dose of cilostazol within 24 h after acute stroke symptoms, then 100 mg twice daily until day 90 post-stroke, or a 180 mg loading dose of ticagrelor during the first 24 h, followed by 90 mg twice daily from day 2 to day 90. Both groups received an open-label 300 mg loading dose of aspirin during the first 24 h, then 75 mg once daily. We followed up with our patients for 3 months. RESULTS: 857 patients completed the 3-month follow-up study 34 (7.6%) patients in the cilostazol group and 29 (6.4%) patients in the ticagrelor group experienced a new stroke (either hemorrhagic or ischemic) (HR 1.37; 95% CI, 0.84-2.26; -value = 0.21), and 44 (9.8%) patients in the cilostazol group and 40 (8.9%) patients in the ticagrelor group experienced a composite of a new stroke, myocardial infarction (MI), or death due to vascular insults (HR 1.11; 95% CI, 0.64-1.93; -value = 0.30). Fifteen (3.3%) patients in the cilostazol arm and 30 (6.7%) patients in the ticagrelor arm experienced drug-related hemorrhagic complications (HR 0.32; 95% CI, 0.19-0.68; -value = 0.01). CONCLUSION: Combining cilostazol with aspirin in large-vessel occlusion minor ischemic stroke or TIA was as effective as ticagrelor and aspirin in preventing recurrent stroke, MI, and death due to vascular events, but resulted in significantly lower rates of hemorrhagic complications.
Maes L, Walsh C, Weimar C
… +18 more, Purroy F, Price C, Clarke B, Castro P, Czlonkowska A, Cuadrado-Godia E, Fischer U, Fonseca AC, Hill MD, Jatuzis D, Kõrv J, Kruuse C, Mikulik R, Nederkoorn PJ, Sztriha L, Thieme M, Kelly P, Lemmens R
Int J Stroke
· 2025 Dec · PMID 41328787
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BACKGROUND: The Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) trial evaluated long-term treatment with colchicine for the prevention of major adverse cardiovascular events (MAC...BACKGROUND: The Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) trial evaluated long-term treatment with colchicine for the prevention of major adverse cardiovascular events (MACE) in a stroke population. Although the intention-to-treat analysis did not demonstrate a significant reduction in the primary endpoint, fewer outcome events were observed in the colchicine-treated group. It is unknown if a potential treatment effect is modified by ischemic stroke etiology. AIMS: In this pre-specified secondary analysis, we aimed to evaluate the efficacy of colchicine for prevention of MACE in patients with minor stroke or high-risk transient ischemic attack (TIA) according to index event stroke etiology. METHODS: A total of 3154 patients with recent non-cardioembolic stroke or TIA were randomly assigned to receive colchicine, 0.5 mg daily in addition to guideline-based usual care or usual care alone. The primary endpoint was a composite of first fatal or non-fatal recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Subgroups of patients with large-artery atherosclerosis, small-vessel disease, and cryptogenic stroke were evaluated. RESULTS: A total of 3100 patients were included in the current analysis. The treatment effect did not vary across stroke subtype subgroups (p = 0.64 for interaction). In patients allocated to colchicine versus usual care alone, the primary endpoint occurred in 32 of 260 (12.3%) versus 42 of 263 (16%) patients with large-artery atherosclerosis (hazard ratio (HR), 0.77 (95% CI, 0.48-1.22)); 39 of 419 (9.3%) versus 47 of 435 (10.8%) patients with small-vessel occlusion (HR, 0.87 (95% CI, 0.57-1.34)); and 82 of 877 (9.4%) versus 92 of 846 (10.5%) patients with cryptogenic stroke (HR, 0.89 (95% CI, 0.66-1.12)). CONCLUSIONS: The direction of effect for prevention of recurrent MACE favored colchicine, consistent with randomized trials in coronary disease, regardless of stroke subtype. Future stroke trials should consider selecting patients with evidence of atherosclerosis irrespective of stroke subtype. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02898610.
Li K, Sun D, Wang M
… +12 more, Pu S, Pan Y, Abdalkader M, Liu F, Chen C, Sun P, Yu J, Huo X, Nguyen TN, Miao Z, Han J, ANGEL-ASPECT Investigators
Int J Stroke
· 2026 Jun · PMID 41317114
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BACKGROUND: Randomized studies have demonstrated the efficacy of endovascular therapy (EVT) for acute large vessel occlusion with large infarction. However, the impact of the occlusion site on EVT outcomes remains undere...BACKGROUND: Randomized studies have demonstrated the efficacy of endovascular therapy (EVT) for acute large vessel occlusion with large infarction. However, the impact of the occlusion site on EVT outcomes remains underexplored. METHODS: We conducted this prespecified subgroup analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT) trial. Participants were enrolled within 24 h of symptom onset and had an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 or an infarct core volume of 70-100 mL and were randomly assigned to undergo EVT or standard medical management (MM). All 455 patients were included and categorized into 2 subgroups by whether there was an internal carotid artery occlusion (ICAO) or middle cerebral artery occlusion (MCAO). The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We further assessed the association between onset-to-puncture time (OPT) and outcome in both groups using ordinal logistic regression and tested for an interaction between occlusion site and the effect of EVT. RESULTS: A total of 164 patients (36.0%) had ICAO, while 291 patients (64.0%) had MCAO. The baseline characteristics of patients treated with EVT and MM were comparable in either the ICAO or MCAO groups. EVT benefit was observed in both groups without significant heterogeneity (p for interaction = 0.891). A significant statistic interaction between occlusion site and treatment on any intracranial hemorrhage (ICH) within 48 h was observed (p for interaction = 0.002), with ICAO significantly increasing the risk of ICH compared to MCAO in patients undergoing EVT (ICAO: common OR, 6.34; 95% CI, 2.84-14.16; MCAO: common OR, 2.19; 95% CI, 1.56-3.09). However, the risk of symptomatic ICH was not increased significantly in both groups. For patients with ICAO, when OPT exceeds about 10 h and 10 min, the benefit of EVT compared to MM is not significant. CONCLUSIONS: Although both ICAO and MCAO patients with large infarction could benefit from EVT, EVT increased the risk of any ICH in ICAO patients without increasing the risk of sICH. Longer OPT was associated with poorer EVT efficacy in patients with ICAO.Data access statement:The data supporting the findings of this study are available from the corresponding author upon reasonable request. URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04551664.
D'Anna L, Prandin G, Foschi M
… +22 more, Abu-Rumeileh S, Favruzzo F, Simonetti R, Barba L, Merlino G, Bax F, Faiz A, Otto M, Guan J, Barnard A, Jeffrey L, Dagan J, Dolkar T, Hayton J, Valente M, Gigli GL, Sacco S, Paciaroni M, Chandratheva A, Simister R, Banerjee S, Boon Lim P
Int J Stroke
· 2025 Nov · PMID 41294253
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BACKGROUND: The clinical utility of implantable cardiac monitors (ICMs) for atrial fibrillation (AF) detection following cryptogenic stroke or embolic stroke of undetermined source (ESUS) is well established. However, th...BACKGROUND: The clinical utility of implantable cardiac monitors (ICMs) for atrial fibrillation (AF) detection following cryptogenic stroke or embolic stroke of undetermined source (ESUS) is well established. However, the optimal timing for ICM implantation to maximize diagnostic yield remains uncertain. AIMS: To systematically review the literature and conduct a meta-analysis to determine whether earlier ICM implantation after cryptogenic stroke or ESUS ischemic stroke improves detection rates and reduces the time to AF diagnosis. SUMMARY OF REVIEW: A comprehensive search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception to June 2025, without language restrictions. References of retrieved articles and relevant reviews were manually searched. We included observational studies or randomized trials reporting ICM use in patients with ESUS or cryptogenic stroke/transient ischemic attack (TIA), providing data on AF detection rates and/or timing metrics (stroke-to-ICM interval, ICM-to-AF interval). Two reviewers independently screened studies and extracted data. Disagreements were resolved by consensus or third-party adjudication. Data were extracted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Study-level AF detection rates were modeled using logit-transformed proportions and pooled using random-effects models (REML). Mixed-effects meta-regressions assessed the effect of timing (stroke-to-ICM interval) on AF detection and diagnostic delay, adjusting for ICM monitoring duration. The primary outcomes were pooled AF detection rate and mean time from ICM implantation to AF diagnosis. Timing of implantation was assessed as a continuous and categorical (early, intermediate, delayed) variable. Forty-seven studies ( = 6918 patients) were included. The pooled AF detection rate was 27.3% (95% CI: 24.6-30.2), with substantial heterogeneity ( = 80.8%). Early ICM implantation (<31.5 days from index event) was associated with a higher AF detection rate compared with delayed implantation (30.0% vs 23.7%; = 0.0017), independent of monitoring duration. Stratified meta-regression confirmed that delayed implantation was associated with lower AF detection even after adjusting for ICM duration. For each additional day of delay in ICM implantation, the time from AF diagnosis increased by an additional 0.32 days on average, even after accounting for monitoring duration ( = 0.0007). CONCLUSION: These findings suggest that earlier ICM implantation enhances AF detection after ESUS or cryptogenic stroke and shortens diagnostic delay. Optimizing timing of post-stroke monitoring may improve patient selection for anticoagulation and reduce recurrent stroke risk.CRD 420251064227.
Mazloum MP, Henon H, Coccia A
… +5 more, Labreuche J, Devos P, Almairac F, Dellamonica J, Casolla B
Int J Stroke
· 2025 Nov · PMID 41294218
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BACKGROUND: Management of large cerebellar infarctions with potential malignant evolution is highly heterogeneous across physicians, and recommendations rely on low-evidence studies. AIM: We aimed to perform a systematic...BACKGROUND: Management of large cerebellar infarctions with potential malignant evolution is highly heterogeneous across physicians, and recommendations rely on low-evidence studies. AIM: We aimed to perform a systematic review and meta-analysis on patients with large cerebellar infarction undergoing neurosurgery, to study mortality and functional outcome, according to neurosurgical technique. SUMMARY OF REVIEW: We searched on PubMed and Embase according to pre-defined selection criteria and we assessed their quality according to a predefined risk of bias scale. Our primary outcomes were mortality and functional outcome rates. Favorable outcome was defined as a modified Rankin scale of 0-2, a Glasgow Outcome Scale of 4-5, or a Barthel Index > 90%. Pooled rates were obtained using random effect model and heterogeneity was quantified using statistics. Among 27 included studies (including 1173 patients), we studied the 662 patients undergoing neurosurgery. All studies were retrospective and observational; there was no randomized clinical trial (RCT). The median selection bias score was 5 (IQR, 4-6). Mortality rate was estimated at 18% [95% CI, 13-24%], 58%. Among survivors, 64% achieved a favorable functional outcome [95% CI, 51-77%], 82%. Study design and heterogeneity in patients' characteristics limited a meaningful comparison of mortality and functional outcome according to neurosurgical techniques. CONCLUSION: High-quality evidence on neurosurgical treatment for large cerebellar infarctions remains limited. Our systematic review and meta-analysis, despite moderate risk of bias, suggest that neurosurgery may reduce mortality and improve functional outcomes. These findings support its potential benefit, but RCTs are needed to confirm effectiveness and evaluate best surgical technique.
Lee JS, Cho H, Jee TK
… +17 more, Lee SH, Bang JS, Choi JH, Chong S, Sung Ahn J, Kim JW, Koh EJ, Lee JY, Phi JH, Lee SH, Cho WS, Kim JE, Kim HS, Wang KC, Park JS, Oh SY, Kim SK
Int J Stroke
· 2025 Nov · PMID 41294212
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BACKGROUND: Pregnancy and delivery are known to increase the risk of cerebrovascular events (CVEs) in patients with moyamoya disease (MMD). This study determined the frequency, risk factors, and outcome of CVEs during pr...BACKGROUND: Pregnancy and delivery are known to increase the risk of cerebrovascular events (CVEs) in patients with moyamoya disease (MMD). This study determined the frequency, risk factors, and outcome of CVEs during pregnancy in MMD. METHODS: We conducted a multicenter study involving 171 MMD patients with 196 deliveries across four Korean tertiary institutions between 1990 and 2023. Data on MMD-related clinical, imaging, and operative findings were collected. We analyzed CVEs and pregnancy outcomes, including delivery mode and anesthesia. Univariate and multivariate analyses were performed to identify risk factors for peripartum CVEs. RESULTS: Peripartum CVEs occurred in 5.6% of pregnancies, with intracerebral hemorrhage being the most common, followed by cerebral infarction. CVEs were more common in women diagnosed with MMD during pregnancy (85.7% vs. 2.6% in women diagnosed before pregnancy) and in women who had not completed revascularization before pregnancy or were hemodynamically unstable: 55.6% versus 1.1%. Delivery mode and anesthesia showed no significant association with the occurrence of CVEs. Multivariate analysis revealed that the "non-revascularized or hemodynamically unstable" group remained a significant risk factor for peripartum CVEs (adjusted odds ratio (OR) = 353.23, < 0.001). CVEs resulted in maternal functional impairment in 4 of 11 affected cases (36.4%) and fetal loss in 2 of 11 cases (18.2%). CONCLUSION: This study highlights the protective effect of revascularization on peripartum CVEs and proposes a structured clinical protocol, recommending prepregnancy hemodynamic assessment and neurosurgical consultation. Women diagnosed with MMD during pregnancy and those in the "non-revascularized or hemodynamically unstable" group should be considered a high-risk group for peripartum CVEs.
Lin YN, Viswanathan A, Ogawa EF
… +7 more, Knuiman P, Chang CH, Chan WP, Huang SW, Schneider JC, Bean JF, Yeh TS
Int J Stroke
· 2026 Jun · PMID 41263381
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BACKGROUND: Decreased cardiorespiratory fitness (CRF) is prevalent in stroke patients, and aerobic training can improve CRF in this population. Protein supplementation has been proposed as a strategy to enhance exercise...BACKGROUND: Decreased cardiorespiratory fitness (CRF) is prevalent in stroke patients, and aerobic training can improve CRF in this population. Protein supplementation has been proposed as a strategy to enhance exercise adaptations by promoting muscle protein synthesis, reducing muscle loss, and improving physical function. However, the potential of protein supplementation to further improve CRF during aerobic training among stroke patients remains unclear. This study aims to evaluate the effect of protein supplementation on CRF and physical performance in patients with chronic stroke undergoing aerobic training. METHODS: This multicenter, participant- and assessor-blinded, randomized clinical trial enrolled 114 ambulatory adults with chronic stroke at four teaching hospitals. Participants were randomized to receive protein supplementation (n = 58) or an isocaloric carbohydrate placebo (n = 56) during 30 supervised aerobic training sessions over 10 weeks. The primary outcome was the change in peak oxygen consumption (V̇Opeak, mL/kg/min) at 11 weeks. Secondary outcomes included CRF-related measures, body composition (total lean and fat mass), and physical performance (Short Physical Performance Battery (SPPB), Physical Performance Test, Berg Balance Scale, and Timed Up-and-Go test). RESULTS: Participants had a mean age of 57.2 years, 30% were women, and 87% completed the primary outcome assessment. At the 11-week follow-up, V̇Opeak increased by 1.7 mL/kg/min (95% CI: 1.0-2.4) in the protein group and 1.6 mL/kg/min (95% CI: 0.9-2.3) in the placebo group, with no between-group difference (mean difference, 0.1 mL/kg/min; 95% CI: -0.8 to 1.1; = 0.43). Both groups showed improvements in most CRF-related and physical performance measures. At 20 weeks, the protein group demonstrated greater SPPB improvement (mean difference, 0.7 points; 95% CI: 0.1-1.3; = 0.03) and lower fat mass at 11 weeks (mean difference, -0.6 kg; 95% CI: -1.2 to -0.06; = 0.04). CONCLUSIONS: Protein supplementation during aerobic training did not significantly enhance CRF compared with an isocaloric placebo. These findings warrant further investigation in populations with a broader range of baseline protein intake.
Wang M, Wei Y, Xie X
… +25 more, Pan Y, Wang M, Wang A, Liu D, Zhao Z, Nie X, Duan W, Liu X, Zhang Z, Liu J, Zheng L, Shen S, Zhong C, Xu T, Jiang Y, Jing J, Meng X, Obst K, Chen CS, Li H, Wang Y, Zhang Y, He J, Wang Y, Liu L
Int J Stroke
· 2025 Nov · PMID 41251301
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BACKGROUND: The optimal timing for initiating antihypertensive therapy after acute ischemic stroke (AIS), particularly regarding cognitive outcomes, remains uncertain. This study investigated the association between trea...BACKGROUND: The optimal timing for initiating antihypertensive therapy after acute ischemic stroke (AIS), particularly regarding cognitive outcomes, remains uncertain. This study investigated the association between treatment timing and 3-month cognitive function. METHODS: This prespecified analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) included patients completing 3-month Montreal Cognitive Assessment (MoCA). Participants were randomized to early (immediate) or delayed (day 8) antihypertensive treatment, with MoCA score as primary outcome. RESULTS: A total of 1682 patients completed the cognitive assessment; 823 received early antihypertensive treatment and 859 received delayed treatment. Baseline characteristics were comparable between the two groups. The median MoCA score was 23 in both groups (β, -0.06; 95% CI, -0.16 to 0.03; = .19). In addition, the proportion of individuals with MoCA scores < 25 was similar between the two groups (62% vs 59%; OR, 1.15; 95% CI, 0.95 to 1.40; = 0.16). Exploratory subgroup analyses suggested a potential interaction by prior antihypertensive use, whereby early antihypertensive treatment was associated with worse cognitive outcomes in patients with prior antihypertensive use (OR, 1.34; 95% CI, 1.01-1.77; = 0.03; for interaction = 0.04). CONCLUSIONS: Early antihypertensive initiation did not improve 3-month cognitive outcomes in AIS patients, highlighting the importance of individualized therapy, especially for high-risk PSCI subgroups.
Int J Stroke
· 2025 Dec · PMID 41242982
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BACKGROUND AND AIM: Cerebral venous thrombosis (CVT) is an uncommon but increasingly recognized cause of stroke.Despite its lower incidence than arterial stroke, CVT can cause substantial functional disability and mortal...BACKGROUND AND AIM: Cerebral venous thrombosis (CVT) is an uncommon but increasingly recognized cause of stroke.Despite its lower incidence than arterial stroke, CVT can cause substantial functional disability and mortality and mainly affects younger adults. This review summarizes current treatment strategies, recent advances, and potential future directions. RECENT ADVANCES: Anticoagulation remains the cornerstone of CVT treatment. While vitamin K antagonists (VKAs) have long been the standard, direct oral anticoagulants (DOACs) have recently been demonstrated to be equally safe and effective, and are increasingly used in routine practice. Endovascular therapy is reserved for selected severe cases unresponsive to anticoagulation, although data from randomized trials remain limited. The recently completed DECOMPRESS2 study has provided high-quality data on the outcomes of patients with severe CVT that underwent decompressive surgery. Novel scoring systems, such as DIAS3 and SI(2)NCAL(2)C, have helped facilitate individualized prediction of seizures and long-term outcomes. FUTURE DIRECTIONS: The diagnostic work-up of CVT could be further improved if clinical decision rules, in combination with biomarkers, are developed and validated. Similarly, Artificial Intelligence algorithms that are able to detect signs of CVT on imaging, even when CVT is not suspected, could help to speed up diagnosis of CVT, allowing faster treatment. Novel anticoagulant and fibrinolytic treatments hold promise to rapidly and safely achieve recanalization of the venous system. Finally, multicenter studies should address novel ways to measure outcome after CVT, beyond the modified Rankin Scale. As with all CVT research, international collaboration through academic consortia will be the key to produce evidence-based answers to the burning clinical questions, with the ultimate goal to reduce the global burden of this condition.
Mujanovic A, Olivé-Gadea M, Diana F
… +77 more, Sökeland GC, Seiffge DJ, Geyik S, Senadim S, Cervo A, Salcuni A, Piano M, Moreu M, López-Frías A, Hassan AE, Miller S, Zapata E, de Albóniga-Chindurza A, Bergui M, Molinaro S, Sousa JA, Gomes F, Sargento J, Alexandre A, Pedicelli A, Hofmeister J, Machi P, Scarcia L, Kalsoum E, Cavalcante F, Bala F, Amorim J, Meira T, Ortega-Gutierrez S, Rodriguez-Calienes A, Renieri L, Capasso F, Romano DG, Barcena E, Seoane D, Abdalkader M, Klein P, Nguyen TN, Perry-da-Câmara C, Fragata I, Yavagal D, Charles JH, Rodríguez J, Vega P, Özdemir AÖ, Uysal Kocabas Z, Smajda S, Salman SA, Khalife J, Jovin T, Biraschi F, Ricchetti F, Castro P, Albuquerque L, Siddiqui A, Jaikumar V, Navia P, Ntoulias N, Psychogios M, Velo M, Zamarro J, de Paco G, Zaidat O, Ashouri Y, AlMajali M, Arenillas JF, Sierra A, Romoli M, Marto JP, Yaghi S, Dobrocky T, Gralla J, Fischer U, Ribo M, Tomasello A, Requena M, Kaesmacher J
Int J Stroke
· 2025 Nov · PMID 41235791
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BACKGROUND: The value of intravenous thrombolysis (IVT) prior to endovascular therapy (EVT) with emergent stenting for intracranial atherosclerotic disease (ICAD)-large vessel occlusion (LVO) is unknown. We aimed to inve...BACKGROUND: The value of intravenous thrombolysis (IVT) prior to endovascular therapy (EVT) with emergent stenting for intracranial atherosclerotic disease (ICAD)-large vessel occlusion (LVO) is unknown. We aimed to investigate the safety and efficacy of IVT among patients with adjuvant intracranial stenting after EVT. METHODS: RESISTANT is a study of consecutive acute ischemic stroke patients who underwent EVT and intracranial stenting from 36 comprehensive stroke centers in 7 countries across 3 continents. The primary outcome of interest was ordinal shift of the modified Rankin Scale (mRS) score at 90 days after the intervention. Secondary outcomes were excellent outcome (mRS 0-1) and functional independence (mRS 0-2) at 90 days. Safety outcomes were rates of symptomatic intracranial hemorrhage (sICH) at 24-hour and 90-day mortality. Adjusted multivariate ordinal and logistic regressions were performed for all outcomes. RESULTS: Of 828 patients (median age 67 years, interquartile range (IQR) 59-77; 65% male), 23% have received IVT. In the adjusted analysis, receiving IVT was not associated with mRS ordinal shift (aOR 0.8, 95% CI 0.6 -1.1), nor with functional independence (aOR 1.1, 95% 0.7-1.7). However, there was a positive association with excellent outcome (aOR 1.6, 95% CI 1.0-2.7). There were no differences in sICH rates at 24-h (aOR 1.5, 95% CI 0.8-2.9), nor 90-day mortality (aOR 0.8, 95% 0.5-1.3). CONCLUSION: In this multi-center study of patients who underwent EVT with emergent intracranial stenting, IVT was associated with excellent clinical outcome, possibly due to indication bias, and there were no safety concerns. Receiving IVT should not be a criterion for deferring acute stenting among patients with ICAD-associated LVO and IVT should not be routinely withheld in suspected ICAD cases.
Pantoja-Ruiz C, Liu L, Lim E
… +12 more, Soley-Bori M, Kalansooriya W, Emmett E, Douiri A, Wang Y, Bhalla A, Khanolkar AR, Parmar D, Landau S, O'Connell MD, Wolfe CDA, Marshall IJ
Int J Stroke
· 2026 Jul · PMID 41222083
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BACKGROUND: Socioeconomic status (SES), often measured by education, income, occupation, or area-level deprivation, impacts stroke incidence and outcomes, yet the underlying mechanisms remain unclear. This review synthes...BACKGROUND: Socioeconomic status (SES), often measured by education, income, occupation, or area-level deprivation, impacts stroke incidence and outcomes, yet the underlying mechanisms remain unclear. This review synthesizes causal analyses quantifying drivers of these inequalities. METHODS: We conducted a systematic review (PROSPERO CRD42024554285) and reported following the PRISMA-2020 guidelines. Observational studies applying causal mediation analysis between SES and stroke risk, disability, or mortality were included from PubMed, Embase, Scopus, and Google Scholar. SES indicators, outcomes, mediators, and decompositions into natural direct effect (NDE) and natural indirect effect (NIE) were extracted. Risk of bias and certainty of evidence were assessed using ROBINS-E and GRADE. A narrative synthesis was undertaken, and findings were illustrated in causal diagrams. RESULTS: Of 12,034 records, 19 studies (15 in high-income countries) were included. Lower SES increased stroke incidence through hypertension (NIE 14-21% of the total effect, moderate certainty), although one study restricted to women reported smaller effects (2-4%). Smoking (6-19.9%, very low certainty). At 3 months post-stroke, the combined outcome of death or disability was higher due to severe strokes (38.5% for ischemic, 57-94% for hemorrhagic, moderate certainty). One study found that hypertension, atrial fibrillation, and smoking together mediated 28.5% of the SES effect on stroke severity (low certainty). Reduced access to thrombolysis and stroke units mediated 2.7% of 3-month disability/mortality (very low certainty), while greater distance to specialized centers explained 48% of inequalities in thrombectomy access (low certainty). Long-term mortality (⩾6 months) was mediated by comorbidities (18%) and healthcare coverage (24-55%), both with low certainty. CONCLUSIONS: Hypertension, smoking, and differential stroke severity at presentation are the main pathways through which low SES increases stroke risk and causes worse outcomes. Targeting these may reduce inequalities, though evidence from low-income settings and emerging mediators (e.g. early-life SES, environmental exposures, care quality) is lacking.
Lioutas VA, Katsanos AH, Palaiodimou L
… +11 more, Theodorou A, Ellul J, Karapanayiotides T, Safouris A, Kargiotis O, Manios E, Giannopoulos S, Themistocleous M, Vadikolias K, Mitsias PD, Tsivgoulis G
Int J Stroke
· 2026 Jun · PMID 41217260
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BACKGROUND: Despite stroke being a leading cause of mortality in Greece, long-term national data on stroke mortality trends remain limited. This study aimed to describe trends in stroke mortality in Greece between 2001 a...BACKGROUND: Despite stroke being a leading cause of mortality in Greece, long-term national data on stroke mortality trends remain limited. This study aimed to describe trends in stroke mortality in Greece between 2001 and 2021, accounting for demographic shifts and changes in care delivery, using nationwide mortality and population data. METHODS: We analyzed cause-of-death data from the Hellenic Statistical Authority (ELSTAT) for 2001-2021. Stroke deaths were defined using International Classification of Diseases, Ninth Revision (ICD-9) (430-438) and Tenth Revision (ICD-10) (I60-I69, G45x) codes. Crude and age-standardized mortality rates (using the GBD 2019 standard) were computed annually and stratified by sex. Negative binomial regression was used to estimate the average annual percent change (AAPC) in mortality. Sex-specific trends, age-specific rate ratios, and time interactions were examined. A decomposition analysis using the Das Gupta method was conducted to quantify the contribution of population aging versus changes in age-specific stroke mortality. RESULTS: Between 2001 and 2021, crude stroke mortality declined from 171.1 to 116.5 per 100,000, and age-standardized mortality declined from 90.5 to 36.4 per 100,000. Crude mortality remained higher in women, but age-standardized mortality was consistently lower compared with men. The female advantage in age group-specific stroke mortality has narrowed over time and reversed in the ⩾80 age group where females experience higher mortality than men. The estimated AAPC for the overall population was -1.90%, corresponding to approximately 292 fewer stroke deaths per year. Decomposition analysis revealed that improvements in age-specific mortality outweighed the adverse effects of population aging. CONCLUSION: Despite substantial population aging and rising crude all-cause mortality, stroke mortality in Greece has declined significantly over the past two decades. This trend likely reflects improvements in acute stroke care and reduced case fatality, rather than a decrease in incidence. Although recent efforts have expanded access to acute reperfusion therapies and stroke units, further gains are possible. Continued investment in national stroke systems and implementation of a comprehensive stroke registry are essential for sustaining and accelerating progress.Data access statement:The study utilized publicly available aggregate data (https://www. STATISTICS: gr/en/home).
Ababneh GE, Yassin A, Allahham M
… +6 more, Alawneh K, Hamed S, Alomari SA, Jaradat MB, Alkhawaldeh A, Almbaidin A
Int J Stroke
· 2025 Nov · PMID 41201080
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BACKGROUND: Atrial fibrillation (AF) detected after stroke or transient ischemic attack (AFDAS) is a critical but often underdiagnosed condition with implications for secondary stroke prevention. This distinctive type of...BACKGROUND: Atrial fibrillation (AF) detected after stroke or transient ischemic attack (AFDAS) is a critical but often underdiagnosed condition with implications for secondary stroke prevention. This distinctive type of AF is increasingly studied to provide a more comprehensive understanding of its complex pathophysiology, which may involve both cardiogenic mechanisms and stroke-induced autonomic dysfunction, a concept known as the neurogenic hypothesis. This study aims to identify the prevalence and predictors of AFDAS to help refine monitoring strategies and improve patient outcomes. METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We included English-language retrospective and prospective cohort studies published from January 1999 to January 2025, analyzing data from 91 studies for prevalence and 54 studies for predictors. We categorized AF detection by different monitoring methods, including electrocardiogram (ECG), Holter monitoring, external loop recorders, and implantable cardiac monitors (ICM). Predictors were grouped into demographic, cardiogenic, neurogenic, and laboratory factors. RESULTS: The overall prevalence of AFDAS varied significantly based on monitoring technique. The pooled prevalence was 7% (95% CI 4.6-10.5) by emergency room ECG, 12.7% (95% CI 9-17.8) by inpatient ECG, 11.9% (95% CI 7.8-17.9) by continuous ECG monitoring, 11.5% (95% CI 8-16.1) by external loop recording, 5.1% (95% CI 2.6-9.7) by Holter monitor, 21.3% (95% CI 18.3-24.7) by ICM, and 17.2% (95% CI 10-28.1) by multiple monitoring methods. Key predictors of AFDAS included older age, female sex, hypertension, chronic kidney disease, left atrial enlargement, advanced interatrial block, and higher NIHSS scores. Insular involvement and major strokes were strongly associated with AF detection, supporting the neurogenic hypothesis. Elevated N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and B-type Natriuretic Peptide (BNP) levels were also linked to a higher AF risk. CONCLUSION: AFDAS is a frequent but variably detected condition, with its prevalence strongly dependent on monitoring duration and modality. Identifying high-risk patients using a combination of clinical, cardiogenic, neurogenic, and laboratory markers can optimize screening strategies and early anticoagulation initiation, potentially reducing stroke recurrence. Future research should focus on refining risk scores integrating neurogenic and cardiogenic markers to guide personalized monitoring approaches and to define the distinct characteristics of AFDAS from known atrial fibrillation (KAF).
Garbuio PA, Fasolin C, Bernard A
… +8 more, Duloquin G, Leclercq T, M'Rabet S, Bamdé CC, Comby PO, Ricolfi F, Béjot Y, Guenancia C
Int J Stroke
· 2025 Nov · PMID 41201071
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BACKGROUND: Timely identification of stroke etiology is crucial in managing large vessel occlusion (LVO) strokes. However, a substantial proportion remains cryptogenic despite comprehensive workup, raising concern about...BACKGROUND: Timely identification of stroke etiology is crucial in managing large vessel occlusion (LVO) strokes. However, a substantial proportion remains cryptogenic despite comprehensive workup, raising concern about underdiagnosed cardioembolic sources. This study assessed the diagnostic contribution of early combined brain-cardiac CT imaging in patients with LVO stroke and explored imaging markers associated with each etiological subtype. METHODS: A total of 252 consecutive patients admitted for LVO stroke who underwent standardized acute-phase brain and cardiac CT imaging were included. Patients were classified as atheromatous, cardioembolic, or cryptogenic LVO stroke before and after consideration of cardiac CT results. Clinical and imaging characteristics of patients were compared according to final causes of stroke. RESULTS: Cardiac CT led to etiological reclassification in 8 patients (3.2%), including 7 cryptogenic cases upgraded to cardioembolic due to detection of intracardiac thrombi in the absence of atrial fibrillation. Patients with cardioembolic LVO stroke (n = 137, 54%) were older, more frequently women, and had higher left atrial surface areas and volumes compared to atheromatous (n = 40, 16%) and cryptogenic cases (n = 75, 30%). Epicardial adipose tissue volume was highest in atheromatous strokes, while cryptogenic cases lacked markers of atrial cardiomyopathy. At follow-up, mortality was highest in the cardioembolic group. CONCLUSION: Early brain-cardiac CT imaging enhances etiological classification in LVO strokes by identifying intracardiac thrombi and other cardioembolic markers missed by standard workup. A substantial subset of cryptogenic LVO strokes may represent a distinct pathophysiological entity. Broader adoption of cardiac CT could inform targeted stroke prevention strategies.